Exploring the Immune Response to SARS-CoV-2 COVID-19 Vaccines in Patients With Relapsing Multiple Sclerosis (RMS) Treated With Ofatumumab (KYRIOS)

Tracking the Immune Response to SARS-CoV-2 modRNA Vaccines in an Open-label Multicenter Study in Participants With Relapsing Multiple Sclerosis Treated With Ofatumumab s.c. (KYRIOS)

This study aimed to understand whether patients with relapsing multiple sclerosis (RMS) can mount an immune response to SARS-CoV-2 mRNA vaccines (initial vaccinations or booster vaccines) when vaccinated either before initiation of ofatumumab treatment or at least 4 weeks after commencing ofatumumab treatment.

Study Overview

• Status: Completed
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Ofatumumab

Detailed Description

This was a four cohort, multicenter, open-label, prospective study of 34 (optionally up to 60) patients who had relapsing multiple sclerosis (RMS) planning to undergo a SARS-CoV-2 mRNA vaccination (initial vaccinations or booster vaccines) as part of clinical routine. The maximal duration of the study for an individual patient was 22 months.

• The first cohort was RMS patients receiving SARS-CoV-2 mRNA vaccine (initial vaccinations or booster vaccines) as part of clinical routine prior to starting ofatumumab treatment.
• The second cohort was participants receiving SARS-CoV-2 mRNA vaccine (initial vaccinations or booster vaccines) as part of clinical routine while already stable on ofatumumab treatment for at least 4 weeks (since first dose).

Cohort 1a - Patients received first SARS-CoV-2 vaccination within the study prior to starting ofatumumab treatment.

Cohort 1b - Patients had already completed initial vaccination cycle and received a booster vaccine within the study prior to starting ofatumumab treatment.

Cohort 2a - Patients who received their first SARS-CoV-2 vaccination within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).

Cohort 2b - Patients who had already completed their initial vaccination cycle and received a booster vaccine within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).

Development of SARS-CoV-2 specific T-cells and functional anti-SARS-CoV-2 antibodies were investigated for up to 18 months after the participants' vaccination.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Bielefeld, Germany, D 33647
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Erbach, Germany, 64711
    • Novartis Investigative Site
  • Siegen, Germany, 57076
    • Novartis Investigative Site
  • Unterhaching, Germany, 82008
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Relapsing Multiple Sclerosis (RMS) diagnosis
• eligible for ofatumumab treatment
• willing and eligible to receive SARS-CoV-2 mRNA vaccine

Exclusion Criteria:

• known prior or current COVID-19 infection
• previous treatment with BTK inhibitor or anti-CD20 therapy other than ofatumumab
• no previous vaccination with a non-modRNA SARS-CoV-2 vaccine.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a; Patients received first SARS-CoV-2 vaccination within the study prior to starting ofatumumab treatment.	Drug: Ofatumumab; Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter; Other Names: OMB157
Experimental: Cohort 1b; Patients had already completed initial vaccination cycle and received a booster vaccine within the study prior to starting ofatumumab treatment.	Drug: Ofatumumab; Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter; Other Names: OMB157
Experimental: Cohort 2a; Patients who received their first SARS-CoV-2 vaccination within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).	Drug: Ofatumumab; Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter; Other Names: OMB157
Experimental: Cohort 2b; Patients who had already completed their initial vaccination cycle and received a booster vaccine within the study while already stable on ofatumumab treatment for at least 4 weeks (since the first dose).	Drug: Ofatumumab; Ofatumumab 20 mg s.c. on days 1, 7, 14, week 4 and every 4 weeks thereafter; Other Names: OMB157

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Having Established SARS-CoV-2-specific T Cells After Receiving a modRNA Vaccine	Participants who established SARS-CoV-2-specific T cells as defined by detection of SARS-CoV-2 reactive T-cells, measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix, either 1 month after second dose of vaccine or 1 month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment.	1 month after second dose of vaccine or booster vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Maintained T-cell Response After Receiving a modRNA Vaccine	Participants who maintained detectable SARS-CoV-2 reactive T-cells (measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix) after second dose of vaccine or 6 and 12 months after booster vaccine in participants who received the vaccine before or after starting ofatumumab treatment. First booster vaccination was optional for cohorts 1a and 2a. In cohorts 1b and 2b the time points "Month 1 after Vacc" and "1 Month after booster" are identical.	At Week 1, Months 6, 12 and 18 after second dose of vaccine or 1 Month after 1st booster, 1 Month after 2nd booster
Increase in Specific T-cells After Receiving an modRNA Booster Vaccine	Patients having established SARS-CoV-2-specific T cells as defined by detection of SARS-CoV-2 reactive T-cells, measured by e.g. ELIspot assay from T-cells that were stimulated with SARS-CoV-2 peptide mix 1 month after booster vaccine in participants who received the respective vaccine before or after starting ofatumumab treatment. The fold change of SI from last value before booster to Month 1 is the ratio of SI at Month 1 divided by SI at last value before booster.	Last value before booster to 1 month after booster
Percentage of RMS Participants With Quantifiable Levels of SARS-CoV-2 Serum Functional Antibodies by Visits and Subcohorts (EAS)	Level of SARS-CoV-2 serum functional antibodies were measured by a central laboratory using a neutralizing antibody detection kit.	Baseline, Week 1 after Vacc, Month 1, 6, 12 after Vacc, 1 month after 1st booster, 1 month after 2nd booster
SARS-CoV-2 Specific CD4+ Effector Memory T-cells	Phenotypic description of the cellular immune response was performed at the central laboratory. T-cells were stimulated with SARS-CoV-2 peptide mix and analyzed for IFNg- and IL4 secretion using FACS analysis.	Baseline, Months 1 ,6, 12 and 18 after vaccinationse of vaccine or 1,6 and 12 months after booster vaccine

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2021
• Primary Completion (Actual): May 10, 2022
• Study Completion (Actual): June 13, 2023

Study Registration Dates

• First Submitted: April 29, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Relapsing Multiple Sclerosis; adult; Ofatumumab; MS; COVID-19; RMS; immune response; SARS-CoV-2 mRNA vaccine
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Antineoplastic Agents; Ofatumumab
• Other Study ID Numbers: COMB157GDE01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No